Stem cell transplants have broken new ground in disease research. Many believe that stem cells are the keys capable of unlocking treatments for some of the world's most devastating diseases, including cancer, multiple sclerosis, Alzheimer's disease, spinal cord injuries and Parkinson's disease. However, the benefits and successes of stem cell research are often overshadowed by moral and ethical considerations because the most versatile stem cells used in research and treatments originate from human embryos or aborted fetal tissues. These ethical concerns are often weighed against the ability of stem cells to revolutionize the practice of medicine and improve the quality and length of life. The potential answers and treatments stem cells promise have spurred many research efforts, even in the face of moral and ethical concerns.
Initially, pluripotent stem cells were isolated and developed from two sources: directly from the inner cell mass of human embryos at the blastocyst stage and from fetal tissue obtained from terminated pregnancies. However with the significant advantages to be gained from use of stem cells, researchers have been searching for a source of these cells, in adults, that would allow them to avoid the ethical debate associated with the use of stem cells derived from embryos and fetal tissues. Multipotent stem cells have not been found for all types of adult tissue, but discoveries in this area of research are increasing. For example, until recently, it was thought that stem cells were not present in the adult nervous system, but in recent years, neuronal stem cells have been isolated from the adult rat and mouse nervous systems.
While the possibility of deriving stem cells from adult tissue sources holds real promise, there are also some significant limitations. First, adult stem cells are often present in only minute quantities, are difficult to isolate and purify, and their number may decrease with age. Further, although stem cells have been isolated from diverse regions of the adult central nervous system (CNS), they cannot be removed from any of these locations without serious consequences to the donor (A. Gritti, et. al., 1996; V. G. Kukekov, et al., 1997).
Due to the difficulties associated with deriving stem cells from adult tissues, typically fetal and neonatal olfactory bulbs have been used as a source of cells for transplantation into regions of the nervous system. (See for example, Njenga, M. K and M. Rodriguez, 1998; Rao, M. S., 1999; R. Tennent, and M. I. Chuah, 1996; Li, Y, et. al., 2000). For example, Archer et al., transplanted fetal glial cells into the canine CNS and showed that the transplanted cells caused a large scale remyelination of demyelinated cells and long term survival of these cells. Archer et al compared results achieved by transplanting fetal cells with those achieved by transplanting adult cells and found that the fetal cells were more capable of remyelination and survived longer. (Archer et. al., 1997).
Other researchers have avoided the ethical debate of using embryonic and fetal stem cells by using other cells and tissues, and more specifically by using adult olfactory bulb tissue, isolated from the brain, for spinal cord repair. For example, Li et al. grafted ensheathment cells from the olfactory bulb into a damaged spinal cord and enabled regeneration of corticospinal tract neurons in the region of the graft (Li, Y., et. al., 2000). Ramon-Cueto et. al. have shown that olfactory bulb ensheathment cells, removed from the bulb, help regenerating spinal cord axons cross a gap in the spinal cord (Ramon-Cueto et. al., 1998). Doucette found that ensheathing cells can adopt several different roles as the need arises. Specifically they are able to switch their phenotype from that resembling an astrocyte to that of a myelinating Schwann cell (R. Doucette, 1995).
The unique regenerative capacity of olfactory neuroepithelium (ONe), found in the nasal cavity, has been well documented in numerous reports. The presence of a stem cell population in ONe with the capacity to produce both neurons and their ensheathment and supporting cells is well known (A. L. Calof, et. al., 1998). Still the difficulty has not been in knowing where adult stem cells are but rather in actually locating and isolating adult stem cells, and maintaining them in a mitotically active state. Others have established cultures of viable stem cells from various sources including embryonic mice (A. L. Calof et. al., 1989, 1998), embryonic rats (A. Kalyani, et. al., 1997; T. Mujaba et. al., 1998; M. S. Rao et. al., 1998; and L. S. Shihabuddin et al., 1997) and neonatal mice and rats (N. K. Mahanthappa et. al., 1993; J. K. McEntire et. al., 2000; S. K. Pixley, 1992, 1994; and M. Satoh and M. Takeuchi, 1995). Cultures from adult mice and rats, (A. L. Calof, et. al., 1998, 1989; F. Feron, et. al., 1999; A. Gritti, et. al., 1996; E. D. Laywell, et. al., 1999; N. Liu, et. al., 1998; K. P. A. Mac Donald, et. al., 1996; and J. S. Sosnowski, et. al., 1995) human embryos, (A. L. Vescovi et. al., 1999) biopsies from patients with Alzheimer's disease (B. Wolozin et. al., 1993) and normal human adults (F. Feron, et. al., 1999; W. Murrel, et. al., 1996; and B. Wolozin, et. al., 1992) have produced viable ONe cultures but none have produced stem or neurosphere-forming cells. Instead, each of these cultures contained committed neurons, glia and epithelial cells.
Therefore identifying a source of readily accessible adult autologous neural stem cells that can be obtained without permanent damage to the donor individual would be of great benefit not only because it avoids the ethical concerns associated with using embryonic and fetal stem cells, but also by providing powerful tools for developing treatments, increasing the successes of transplantation techniques, and by providing methods for diagnostic and drug development evaluations.